Nitric oxide inhibits rat intestinal secretion by Clostridium difficile toxin A but not Vibrio cholerae enterotoxin

Background & Aims: Intestinal inflammation is associated with increased synthesis of nitric oxide, whereas inhibition of NO synthase (NOS) reduces experimental chronic intestinal inflammation. The aim of this study was to test the effects of NO blockers and donors on acute intestinal inflammation induced by Clostridium difficile toxin A in rat ileum. Methods: Rats received NOS inhibitors or NO donors before measurement of toxin-mediated ileal secretion and permeability changes. Mucosal mast cell and neutrophil activity were measured by release of vat mast cell protease II and myeloperoxidase activity, respectively. Results: NOS inhibitors augmented but an NO donor inhibited toxin A-mediated ileal secretion and permeability when given before but not after toxin administration. Neither an NOS inhibitor nor an NO donor had any effect on cholera toxin-mediated secretion. Mast cell degranulation and neutrophil infiltration occurred after injection of toxin A or an NOS inhibitor, whereas the NO donor blocked both toxin A effects. Conclusions: NOS inhibitors augmented and an NO donor blocked the intestinal effects of toxin A but not of cholera toxin. NO protects against toxin A by inhibition of intestinal mast cells and neutrophils, which are activated by toxin A, but not by cholera toxin.